US2003176434A1PendingUtilityA1

Compounds and methods for promoting smoking cessation

Assignee: RES TRIANGLE INSITUTEPriority: Nov 8, 2000Filed: Jan 7, 2003Published: Sep 18, 2003
Est. expiryNov 8, 2020(expired)· nominal 20-yr term from priority
Inventors:F. Ivy Carroll
A61P 43/00A61P 25/18A61P 25/08A61P 25/28A61P 25/34A61P 3/04A61P 25/24A61P 25/22A61P 25/00A61P 25/16A61P 25/04A61K 31/4439C07D 487/22A61P 1/04A61K 31/44
52
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Claims

Abstract

Compounds and methods for promoting smoking cessation. The compounds may be used to treat a variety of other conditions and disease states.

Claims

exact text as granted — not AI-modified
1 . A method of training a smoker to quit smoking, comprising administering to a smoker in need thereof an effective amount of a compound represented by formula (I):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are each, independently, H, —OH, —N(R)C(═NR)N(R) 2 , or —N(R) 2 ;  
 or  
 A 1  and A 2  together form ═O, ═NOR, ═NR, —O—NR—, —NR—O—, or —NR—NR—;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . The method of  claim 1 , wherein A, and A 2  are each, independently, H, —OH, —N(R)C(═NR)N(R) 2 , or —N(R) 2 .  
     
     
         3 . The method of  claim 1 , wherein A, and A 2  together form ═O, ═NOR, ═NR, —O—NR—, —NR—O—, or —NR—NR—.  
     
     
         4 . The method of  claim 1 , wherein one of A 1  and A 2  is —NH 2  and the other is H.  
     
     
         5 . The method of  claim 1 , wherein A 1  and A 2  together form ═NOH or ═NOCH 3 .  
     
     
         6 . The method of  claim 1 , wherein one Q is N.  
     
     
         7 . The method of  claim 1 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         8 . The method of  claim 1 , wherein R is H, alkyl or benzyl.  
     
     
         9 . The method of  claim 1 , wherein at least one X is aryl.  
     
     
         10 . The method of  claim 9 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         11 . The method of  claim 1 , wherein the compound is represented by formula (Ia):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are as defined in  claim 1;   
 X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 1;  and  
 R is as defined in  claim 1 .  
 
     
     
         12 . The method of  claim 1 , wherein the compound is represented by formula (Ib):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are as defined in  claim 1;   
 X 1 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 1;  and  
 R is as defined in  claim 1 .  
 
     
     
         13 . The method of  claim 1 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ) n —Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         14 . A method of training a smoker to quit smoking, comprising administering to a smoker in need thereof an effective amount of a compound represented by formula (II):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is —R, —N(R) 2 , —C(═NR)N(R) 2  or —OR;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         15 . The method of  claim 14 , wherein A 3  is H or alkyl.  
     
     
         16 . The method of  claim 14 , wherein A 3  is H.  
     
     
         17 . The method of  claim 14 , wherein one Q is N.  
     
     
         18 . The method of  claim 14 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         19 . The method of  claim 14 , wherein R is H, alkyl or benzyl.  
     
     
         20 . The method of  claim 14 , wherein at least one X is aryl.  
     
     
         21 . The method of  claim 20 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         22 . The method of  claim 14 , wherein the compound is represented by formula (IIa):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is as defined in  claim 14;   
 X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 14;  and  
 R is as defined in  claim 14 .  
 
     
     
         23 . The-method of  claim 14 , wherein the-com-pound is represented by formula (IIb):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is as defined in  claim 14;   
 X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 each S is, independently, halogen, alkyl, alkenyl, alkynyl, phenyl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN, or  
 two S, taken together with the phenyl group to which they are bonded, form a 2-naphthyl group;  
 Y is a halogen; and  
 c is 0, 1, 2, 3, 4 or 5.  
 
     
     
         24 . The method of  claim 14 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ) n —Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         25 . A method of training a smoker to quit smoking, comprising administering to a smoker in need thereof an effective amount of a compound represented by formula (III):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is —(CH 2 ) m —, —O—, —NR—, —(CH 2 ) m —O—, —O—(CH 2 ) m —, —(CH 2 ) m N(R)—, —N(R)(CH 2 ) m —, —C(═NR)—, —(CH 2 ) m S—, —(CH 2 ) m CH═CH—, or —(CH 2 ) m C≡C—;  
 m is 1, 2, 3 or 4;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         26 . The method of  claim 25 , wherein Z is —CH 2 —.  
     
     
         27 . The method of  claim 25 , wherein one Q is N.  
     
     
         28 . The method of  claim 25 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         29 . The method of  claim 25 , wherein at least one X is aryl.  
     
     
         30 . The method of  claim 25 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         31 . The method of  claim 25 , wherein the compound is represented by (IIa):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is as defined in  claim 25;   
 X 1 , X 2  and X 3  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 R is as defined in  claim 25 .  
 
     
     
         32 . The method of  claim 25 , wherein the compound is represented by formula (IIIb):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is as defined in  claim 25;   
 X 1 , X 2  and X 3  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 R is as defined in  claim 25 .  
 
     
     
         33 . The method of  claim 25 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ) n —Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         34 . A compound represented by formula (I):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are each, independently, H, —OH, —N(R)C(═NR)N(R) 2 , or —N(R) 2 ;  
 or  
 A 1  and A 2  together form ═O, ═NOR, ═NR, —O—NR—, —NR—O—, or —NR—NR—;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         35 . The compound of  claim 34 , wherein A 1  and A 2  are each, independently, H, —OH, —N(R)C(═NR)N(R) 2 , or —N(R) 2 .  
     
     
         36 . The compound of  claim 34 , wherein A, and A 2  together form ═O, ═NOR, ═NR, —O—NR—, —NR—O—, or —NR—NR—.  
     
     
         37 . The compound of  claim 34 , wherein one of A 1  and A 2  is —NH 2  and the other is H.  
     
     
         38 . The compound of  claim 34 , wherein A 1  and A 2  together form ═NOH or ═NOCH 3 .  
     
     
         39 . The compound of  claim 34 , wherein one Q is N.  
     
     
         40 . The compound of  claim 34 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         41 . The compound of  claim 34 , wherein R is H, alkyl or benzyl.  
     
     
         42 . The method of  claim 34 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ), —Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         43 . The compound of  claim 34 , wherein the compound is represented by formula (Ia):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are as defined in  claim 34;   
 X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 34;  and  
 R is as defined in  claim 34 .  
 
     
     
         44 . The compound of  claim 34 , wherein at least one X is aryl.  
     
     
         45 . The compound of  claim 44 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         46 . The compound of  claim 34 , wherein the compound is represented by formula (Ib):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 1  and A 2  are as defined in  claim 34;   
 X 1 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN; and  
 R is as defined in  claim 34;   
 Y is as defined in  claim 34;   
 each S is, independently, halogen, alkyl, alkenyl, alkynyl, phenyl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN, or  
 two S, taken together with the phenyl group to which they are bonded, form a 2-naphthyl group; and  
 c is O, 1, 2, 3, 4 or 5  
 
     
     
         47 . A compound represented by formula (II):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is —R, —N(R) 2 , —C(═NR)N(R) 2 , or —OR;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN, with the proviso that at least one X is aryl;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         48 . The compound of  claim 47 , wherein A 3  is H or alkyl.  
     
     
         49 . The compound of  claim 47 , wherein A 3  is H.  
     
     
         50 . The compound of  claim 47 , wherein one Q is N.  
     
     
         51 . The compound of  claim 47 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         52 . The compound of  claim 47 , wherein R is H, alkyl or benzyl.  
     
     
         53 . The compound of  claim 47 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         54 . The method of  claim 47 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ) n —Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         55 . The compound of  claim 47 , wherein the compound is represented by formula (IIa):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is as defined in  claim 47;   
 X 1 , X 2 , X 3  and X 4  are X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 47;  and  
 R is as defined in  claim 47 .  
 
     
     
         56 . The compound of  claim 47 , wherein the compound is represented by formula (IIb):  
       
         
           
           
               
               
           
         
       
       wherein 
 A 3  is as defined in  claim 47;   
 X 1 , X 2 , X 3  and X 4  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 R is as defined in  claim 47;   
 Y is as defined in  claim 47;   
 each S is, independently, halogen, alkyl, alkenyl, alkynyl, phenyl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN, or  
 two S, taken together with the phenyl group to which they are bonded, form a 2-naphthyl group; and  
 c is 0, 1, 2, 3, 4 or 5.  
 
     
     
         57 . A compound represented by formula (III):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is —(CH 2 ) m —, —O—, —NR—, —(CH 2 ) m —O—, —O—(CH 2 ) m —, —(CH 2 ) m N(R)—, —N(R)(CH 2 ) m —, —C(═NR)—, —(CH 2 ) m S—, —(CH 2 ) m CH═CH—, or —(CH 2 ) m C≡C—;  
 m is 1, 2, 3 or 4;  
 each Q is, independently, C—X or N, with the proviso that at least one Q is N and at least one Q is C—X;  
 each X is, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is a halogen; and  
 each R is, independently, H, alkyl, alkenyl, alkynyl, aryl, or aralkyl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         58 . The compound of  claim 57 , wherein Z is —CH 2 —.  
     
     
         59 . The compound of  claim 57 , wherein one Q is N.  
     
     
         60 . The compound of  claim 57 , wherein each X is independently selected from the group consisting of H, F, Cl, Br, I, CH 3 , OH, NH 2 , (CH 3 ) 2 N, NHAc, CF 3 SO 3 , unsubstituted phenyl, phenyl substituted with a substituent selected from the group consisting of nitro and methoxy.  
     
     
         61 . The compound of  claim 57 , wherein at least one X is aryl.  
     
     
         62 . The compound of  claim 61 , wherein said aryl is unsubstituted phenyl or phenyl substituted with one or more substituents selected from the group consisting of halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY and —CN.  
     
     
         63 . The method of  claim 57 , wherein said alkyl group in the definition of R is represented by the formula —(CH 2 ).—Y, wherein Y is a halogen and n is an integer from 1 to 8.  
     
     
         64 . The compound of  claim 57 , wherein the compound is represented by (IIa):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is as defined in  claim 57;  and  
 X 1 , X 2  and X 3  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 57;  and  
 R is as defined  claim 57 .  
 
     
     
         65 . The compound of  claim 57 , wherein the compound is represented by formula (IIIb):  
       
         
           
           
               
               
           
         
       
       wherein 
 Z is as defined in  claim 57;   
 X 1 , X 2  and X 3  are each, independently, H, halogen, alkyl, alkenyl, alkynyl, aryl, aralkyl, —OH, —OR, —CH 2 —CO 2 R, —CO—R, —CO 2 R, —N(R) 2 , —NR—CO—R, —CO—N(R) 2 , —NRCO 2 R, —SO 3 CF 3 , —NO 2 , —N 3 , —CF 3 , —CH═CHY, or —CN;  
 Y is as defined in  claim 57;  and  
 R is as defined in  claim 57 .  
 
     
     
         66 . The compound of  claim 34 , which is labeled with at least one labeling atom.  
     
     
         67 . The compound of  claim 47 , which is labeled with at least one labeling atom.  
     
     
         68 . The compound of  claim 57 , which is labeled with at least one labeling atom.  
     
     
         69 . A method of treating a condition selected from the group consisting of Alzheimer's disease, Parkinson's disease, pain, depression, Tourette's syndrome, inflammatory bowel syndrome, schizophrenia, anxiety, epilepsy, attention-deficit hyperactivity disorder, ulcerative colitis and obesity, comprising administering an effective amount of the compound of  claim 34  to a patient in need thereof.  
     
     
         70 . A method of treating a condition selected from the group consisting of Alzheimer's disease, Parkinson's disease, pain, depression, Tourette's syndrome, inflammatory bowel syndrome, schizophrenia, anxiety, epilepsy, attention-deficit hyperactivity disorder, ulcerative colitis and obesity, comprising administering an effective amount of the compound of  claim 47  to a patient in need thereof.  
     
     
         71 . A method of treating a condition selected from the group consisting of Alzheimer's disease, Parkinson's disease, pain, depression, Tourette's syndrome, inflammatory bowel syndrome, schizophrenia, anxiety, epilepsy, attention-deficit hyperactivity disorder, ulcerative colitis and obesity, comprising administering an effective amount of the compound of  claim 57  to a patient in need thereof.

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